Dynamic Inflammatory and Mood Predictors of Cognitive Aging in Bipolar Disorder

描述（由申请人提供）：随着人口老龄化，严重精神疾病，如双相情感障碍（BD）对认知和健康的影响给个人和社会带来的负担将会增加。在许多健康和认知领域，双相障碍的过早和加速衰老轨迹已经开始被认识到，但具体的机制尚未确定，特别是认知衰老的过程。炎症功能的标志物，如细胞因子水平，已知会影响认知，随着年龄的增长而变化，并预测心理健康个体的衰退。细胞因子水平在双相障碍患者中也出现异常，但双相障碍患者的情绪不稳定使得测量炎症和认知测量的短期和长期变化具有挑战性。尽管如此，在这一人群中的研究提供了一个独特的机会，以更好地了解情绪和行为失调程度的变化如何调节或调节免疫-认知关联。我们建议使用创新的多队列突发纵向设计（MBLD）来表征认知和炎症反应的轨迹，并确定：1)短期内认知和炎症之间的关系，同时考虑情绪变异性的影响；2)炎症标志物短期变异性的基线测量和水平，可能预测认知变化的长期轨迹；3)炎症、认知和情绪变量之间的长期关系（即变化机制）。我们将评估144名成年人（35-60岁）的临床相关情绪失调症状，如双相情感障碍I诊断，以及115名年龄相似的无精神疾病的非双相情感障碍比较（NC）参与者。认知、细胞因子水平和情绪（以及其他潜在的影响变量）

DESCRIPTION (provided by applicant): As the population ages, the burden on individuals and society due to the cognitive and health effects of serious mental illnesses, such as bipolar disorder (BD), will increase. Premature and accelerated aging trajectories in BD are beginning to be recognized in many health and cognitive domains, but specific mechanisms have not yet been identified, particularly for the course of cognitive aging. Markers of inflammatory function, such as cytokine levels, are known to affect cognition, change with age, and predict declines in mentally healthy individuals. Cytokine levels also appear to be abnormal in those with BD, but mood instability in BD makes measurement of short- and long-term changes in both inflammatory and cognitive measures challenging. Nonetheless, studies within this population afford a unique opportunity to better understand how variations in the degree of emotional and behavioral dysregulation may moderate or mediate immune-cognitive associations. We propose to use an innovative multi-cohort burst longitudinal design (MBLD) to characterize trajectories of cognitive and inflammatory response and identify: 1) relationships between cognition and inflammation in the short term while accounting for effects of mood variability, 2) baseline measures and levels of short-term variability in inflammatory markers that might predict long-term trajectories of cognitive change, and 3) relationships between inflammatory, cognitive, and mood variables in the long-term (i.e., mechanisms of change). We will assess 144 adults (35-60 years old) with clinically-relevant symptoms of mood dysregulation, as indicated by Bipolar I diagnosis, and 115 similarly aged non-BD comparison (NC) participants without mental illnesses. Cognition, cytokine levels, and mood (along with other potential contributing variables) will be measured weekly or daily over a two week period using intensive remote monitoring and home visits (burst assessment). Burst assessments will be repeated annually (longitudinal assessment) for three years in the BD group, and at one year in the NC group. This project addresses NIMH Strategic Objective # 2: charting mental illness trajectories to determine when, where, and how to intervene. Specifically, using an innovative design that allows us to account for, and measure the impact of, variability in mood symptoms, we can discover inflammatory markers (both static and dynamic) that predict the course of cognitive change among individuals with mood instability. By understanding the complex and dynamic interplay between inflammation, cognition, and mood, pharmacologic and behavioral interventions can be designed to slow or reverse the trajectory of declining function in bipolar disorder.